Association of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) gene polymorphisms with susceptibility to type 2 diabetes

Abstract

Type 2 diabetes (T2D) is defined by high levels of glucose in the blood. The collagen IV level is associated with conditions of hyperglycemia and insulin resistance. Collagen type IV α3 chain (COL4A3) is a structural protein of the extracellular matrix (ECM). Matrix metallopeptidase 9 (MMP-9) is an enzyme that degrades the extracellular matrix and its activity is moderated by TIMP metallopeptidase inhibitor 1 (TIMP-1). The aim of the current study was to examine the association between genetic polymorphisms of COL4A3 (rs55703767), MMP-9 (rs17576) and TIMP-1 (rs6609533) in patients with T2D. This case-control study was performed on 120 Iranian patients with T2D and 120 healthy individuals. Genotypes were analyzed using the amplification refractory mutation system-polymerase chain reaction technique. The findings demonstrated significant differences between genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms as follows: COL4A3 (G/T); TT vs. GG, odds ratio (OR)=0.235, 95% confidence interval (CI)=0.063-0.0802 (P=0.013) and T vs. G, OR=0.592, 95% CI=0.371-0.943 (P=0.026); MMP-9 (A/G); AG vs. GG, OR=2.429, 95% CI=1.232-4.820 (P=0.008) and A vs. G, OR=2.176, 95% CI=1.155-4.130 (P=0.013). No significant association was identified between TIMP-1 (A/G) polymorphism and T2D in females and males. Thus, the genotypic and allelic distributions of COL4A3 (G/T) and MMP-9 (A/G) polymorphisms were associated with T2D. In addition, no significant association was identified in the genotypic distribution of the TIMP-1 (A/G) gene in females and in males. Further studies in other ethnic groups are required to confirm these findings.